Oxalate, an end product of metabolism, is a major component of 80% of kidney stones, and small changes in its urinary concentration critically influence calcium oxalate crystallization. The high frequency of a family history in "idiopathic" renal stone disease has suggested to some investigators that urolithiasis may be a metabolic disorder characterized by a defect in cellular oxalate transport. Inherited defects in erythrocyte calcium and oxalate transport have been recently identified in patients with kidney stones, strengthening the contention that abnormalities in cellular transport may play a primary role in "idiopathic" calcium stone formation. However, the cellular transport of oxalate has not been characterized in the kidney, particularly in papillary cells where calcium oxalate crystallization usually occurs. The aims of this proposal, thus are; 1. To characterize oxalate transport in renal cortical and papillary cells. 2. To assess alterations in oxalate handling in experimental models of nephrolithiasis that feature nephron dysfunction or injury. These studies will help elucidate the role of nephron dysfunction or injury in the pathogenesis of calcium oxalate nephrololithiasis and may give us insights on how to prevent this disease.